The liver is the most important organ in metabolizing xenobiotics and drugs. Liver cells (hepatocytes) are used frequently in testing drug metabolism and hepatotoxicity. Hepatocytes in culture can form spheroids that exhibit higher liver-specific functions and sustain high viability longer in culture. This proposed research is to develop an integrated system employing hepatocyte spheroids for both screening purposes and for metabolic studies. In phase I studies, we will develop a high throughput screening system suitable for integration with a miniaturized bioartificial liver for such studies. We will also demonstrate genetic metabolic engineering of hepatocyte spheroids. The analysis of the results will be facilitated by the use of a cDNA microarray immobilized with most relevant DNA sequences. The proposed work will fill a critical need for bioassay systems for high throughput screening. PROPOSED COMMERCIAL APPLICATION: This project will develop an integrated bioassay system using hepatocytes. It will greatly facilitate high throughput screening.